The anti-nuclear movement won a crushing victory in Italy on Monday when well over 90% of voters rejected Silvio Berlusconi's plans for a return to nuclear power generation.

The result represented an overwhelming setback for the prime minister, who had tried to thwart the outcome by discouraging Italians from taking part. The referendum needed a turnout of at least 50% to be binding. Interior ministry figures projections indicated that more than 57% of the electorate had taken part. Greenpeace called it a historic result. Quorums were also reached in three other referendums held simultaneously – the first time in 16 years that a quorum had been achieved in any referendum in Italy.

Official projections showed more than 95% of voters rejecting water privatisation and a law allowing Berlusconi and other ministers to cite government business as a reason for delaying trials in which they were defendants. The expected majority against nuclear power was 94%.

For the prime minister it represented a second, bitter setback in under two weeks. His government, which yokes his Freedom People movement to the regionalist and Islamophobic Northern League, first ran into serious trouble on 30 May when his candidate for mayor of Milan lost in a local election runoff. Milan is Berlusconi's home city and traditionally a weather-vane accurately pointing to Italy's future political direction.

Acknowledging defeat even before the polls closed, Berlusconi said: "We shall probably have to say goodbye to nuclear [energy]." He told a press conference in Rome that his government would now throw all its energy into developing renewable sources. The outcome was a huge success for the anti-nuclear movement in the world's first nationwide vote on the issue since Japan's Fukushima disaster. The ballot was also the latest, and most persuasive, evidence that a majority of Italians have turned against their flamboyant prime minister.

The government, which appealed to the courts for the vote to be scrapped, did all it could to keep turnout low. Berlusconi boycotted the vote and Italian television, largely under his sway, almost ignored the approaching ballots until the final days of a poorly funded, low-profile campaign.

Following the defeat in Milan, many rank-and-file Northern League supporters have been urging their leader, Umberto Bossi, to cut himself free of Berlusconi. The party leadership has so far remained wedded to the coalition while pressing for a radical change in economic policy that would deliver tax cuts to its lower middle-class electoral base. But as the results of the two-day ballot became known on Monday, it was clear that even some of the League's top officials were losing patience. Roberto Calderoli, a cabinet minister, said: "In the local elections two weeks ago we took the first hit. Now, with the referendum, has come the second. I would not like taking hits to become a habit."

Italy abandoned its nuclear programme following a similar referendum in 1987. The government of the day opted to phase out all the country's existing plants. The last one shut down in 1990. Berlusconi had planned to generate a quarter of Italy's electricity with French-built nuclear plants. Construction of the first was due to start between 2013 and 2015.

Vittorio Cogliati Dezza, president of the environmental organisation Legambiente, said: "The era of nuclear [energy] is coming to an end today. Definitively. A new season of development for the country is beginning." Recalling Italy's first and most famous legislative referendum in 1974, when voters were asked whether divorce should be outlawed, the leader of the biggest opposition group, Pier Luigi Bersani of the Democratic party, said the latest ballot had also been a referendum on divorce. But this time, said Bersani, it was about "the divorce between the government and the country".